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April 21, 2024

Repurposed skin cells can help treat cancer

By TONY WU | March 10, 2016

A recent breakthrough from researchers at the University of North Carolina at Chapel Hill has shed more light on a potential mechanism of treating cancer. Cancer in its most basic sense is a disease that involves abnormal and uncontrollable cell growth, but its complex biology makes treatment difficult. This challenge has spurred thousands of scientists to explore the mechanisms of cancer and work on developing more effective cures for the disease.

The World Health Organization (WHO) estimates that there were four million new cases of cancer and 8.2 million cancer-related deaths worldwide in 2012. There are over a hundred types of cancer and each is classified by the type of cell that is first affected by the disease. Despite their differences, most cancer cases develop through the same process of initiation, promotion and progression. There are two groups of genes in every cell that are pertinent to the discussion of cancer, proto-oncogenes and tumor suppressor genes. Proto-oncogenes are usually inactivated in a cell, while tumor suppressor genes are expressed in a normal cell. During the initiation stage of carcinogenesis, proto-oncogenes can be activated and tumor suppressor genes can be deactivated, which promotes cancerous behavior such as uncontrolled cell growth. During promotion and progression, these mutated cells proliferate and the number of mutations in the cells increase.

Many factors can impact the degree and severity of these mutations, but there are three main theories of carcinogenesis. The gene mutation theory focuses on the role of gene mutations as the basis for developing cancerous cells. The theory of aneuploidy states that cancer is caused by compounds called carcinogens. The affected cells create daughter cells that have abnormal numbers of chromosomes. The last theory, called the epigenetic theory, states that the normal processes of DNA methylation can introduce mutations that can ultimately cause cancer. Although these three theories diverge widely on their predicted causes of carcinogenesis, many scientists agree that combinations of these theories likely drive the development of cancer.

To treat the wide variety of cancers affecting the population, physicians employ methods such as chemotherapy, radiation and surgery, but increasingly, there has been a movement toward personalized treatment plans. Currently, cancer patients experience a wide range of outcomes even when treated with the same regimens.

To address the need for better treatments, researchers at the University of North Carolina at Chapel Hill developed a treatment that re-programs skin cells, specifically fibroblasts that produce collagen and connective tissue, into induced neural stem cells. This treatment is shown to attack cancer cells more effectively, as one difficulty in treating glioblastoma, or cancer of the brain or spine, is the tendency for the cancer to develop in areas of the brain that are difficult to reach using conventional cancer therapies.

In this experiment, the researchers demonstrated that these induced neural stem cells could move throughout the brain and kill cancer cells that remain after surgery. The researchers also showed that the stem cells can be engineered to produce and deliver tumor-killing proteins as therapeutic agents. By eliminating the remaining cancer cells, there is a greater chance of cancer remission, which increases the patient survival rate.

Though the treatment shows promise, there are still obstacles to overcome. Mainly, the effectiveness of the stem cell treatment in humans has yet to be proven. There is also the existing difficulty of maintaining stem cells in a target without supporting matrices, which are designed to ensure that the stem cells are well-organized and can be retained; without them, the staying power of the cells is low.

Now, the researchers are turning their focus onto human stem cells. They also plan to test whether more effective tumor-killing drugs can be loaded into the tumor-seeking neural stem cells.

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